This grant proposes to study rat intestinal epithelial cell glycosyltransferases and cell membrane glycoproteins in order to determine their role in the control of differentiation. Methods have been established which separate the differentiated villus cell from the undifferentiated crypt cell. Furthermore, intestinal plasma membranes have been purified and separated from a purified Golgi fraction. We propose to utilize these techniques to (1) analyze and characterize the changes in intestinal epithelial cell surface membrane glycoproteins associated with cell turnover, differentiation and tumor induction, (2) characterize the changes in intestinal epithelial cell surface membrane glycoprotein synthesis associated with differentiation and malignant transformation. We will also study animal tumor models we have recently described, where growth of the tumors correlated with the appearance and levels in serum of an electrophoretically distinct peak of galactosyltransferase on polyacrylamide gels (galactosyltransferase isoenzyme II). These animal tumor models will be studied in order to determine the role of cell membrane glycoproteins and tumor glycosyltransferases in tumor growth and metastases. We propose specifically to (1) characterize the biological properties of the tumor-associated serum galactosyltransferase isoenzyme II, and (2) purify and characterize the tumor galactosyltransferases and compare them with normal tissue and the serum isoenzymes. It is hoped that these studies will further define the cell membrane changes peculiar to tumor growth and the ability of a tumor cell to metastasize.